Is TSC2 p.Ile463= (c.1389C>A) pathogenic?

TSC2 p.Ile463= (c.1389C>A) is classified Likely benign in TSC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-31). No allele count reported in gnomAD v4.1 (AN 1,551,348); Associated with tuberous sclerosis 2.

What condition is associated with TSC2 p.Ile463= (c.1389C>A)?

TSC2 p.Ile463= (c.1389C>A) is associated with tuberous sclerosis 2 (ClinVar).

How common is TSC2 p.Ile463= (c.1389C>A) in the general population?

TSC2 p.Ile463= (c.1389C>A) is no allele count reported in gnomAD v4.1 (AN 1,551,348) (gnomAD).

How is Tuberous sclerosis complex inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

TSC2 p.Ile463=

c.1389C>A · rs1188230416 · VCV1092630

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,551,348)

Conditions

tuberous sclerosis 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 0.76, phastCons 1
Overall
CADD	15.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,551,348). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TSC2
Protein: p.Ile463=
Coding: c.1389C>A
MANE Select: NM_000548
dbSNP: rs1188230416
Type: single nucleotide variant
Location: chr16:2062999 (GRCh38)
Gene constraint: LOEUF 0.203 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.81 · 2 PDB
Residue 463: an α-helix; a UniProt-annotated variant site (in)

Full TSC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

tuberous sclerosis 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Tuberous sclerosis complex (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages
Prevalence: 1-9 / 100 000 (Taiwan, Province of China)

Similar variants

TSC2 p.Ile463Ser Uncertain significance ★★ ⚠ same residue
TSC2 p.Ile463Val Benign/Likely benign ★★ same residue
TSC2 p.Ile463Asn Uncertain significance ★ ⚠ same residue
TSC2 p.Ile463Met Conflicting classifications of pathogenicity ★ ⚠ same residue
TSC2 p.Ile463fs Pathogenic same residue
TSC2 c.1257+1G>A Pathogenic ★★ same condition
TSC2 c.1258-2A>G Pathogenic ★★ same condition
TSC2 c.1361+1G>A Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/tsc2-p-ile463 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown